Predicting Future Moderate or Severe Exacerbations in Asthma

Asthma exacerbations are common in the outpatient setting, and the severity — moderate or severe — is largely predicted by experiencing a recent, previous exacerbation of similar intensity. The results, which also indicated that moderate and severe exacerbations represent separate and distinct patient phenotypes, were published in BioMed Central.¹

No single predictive factors for exacerbations have emerged in recent literature, although a number of features, including social factors, asthma control testing, comorbid conditions such as rhinitis, the use of inhaled steroids, and recent experience of severe exacerbation, have all been suggested.^2-11

Researchers from the asthma unit at the Hospital Universitario Virgel del Rocio in Seville, Spain, recruited 330 outpatients between March 2007 and March 2010 (median age, 39.2±16.7 years; 69.7% women). At baseline, more than 80% of the cohort had mild or moderately persistent asthma; 73% had asthma that was poorly controlled. The majority of participants were receiving combination therapy (long-acting beta agonist therapy plus an inhaled corticosteroid). More than 23% reported not regularly using any kind of therapy for asthma control, whereas 25.9% of participants who used asthma control were not using correct inhaler technique.

Over the course of 12 months, 58.5% and 8% of participants experienced moderate or severe exacerbations, respectively. In multivariate analysis, the only significant predictor of future severe exacerbation at both baseline and 4-month follow-up was a previous severe exacerbation (odds ratio [OR], 4.218 [95% CI, 1.536-11.588] at baseline vs OR, 6.889 [95% CI, 2.018-23.512] at 4 months) and inhalation technique (OR, 3.572 at baseline; 95% CI, 1.324-9.638).

Previous moderate exacerbation was the only factor predictive of experiencing moderate exacerbation in the future (OR, 2.909 [95% CI, 1.542-5.489] at baseline vs OR, 1.702 [95% CI, 1.146-2.529] at 4 months). The number of moderate exacerbations occurring during the study year remained consistent with the previous year (OR, 2.909; 95% CI, 1.542-5.489). In patients who experienced a moderate exacerbation at 4 or 12 months, there were significant differences (vs to those who did not experience a moderate exacerbation) in the Global Initiative for Asthma and asthma control test measures of asthma control (P <.001), number of previous moderate exacerbation episodes during the first 4 months of follow-up (P <.001), fractional exhaled nitric oxide (P < .02), previous uncontrolled days (P <.01), and absolute forced expiratory volume at 1 second (P <.05).

The investigators pointed out that the majority of study participants had less severe disease than participants in comparative studies; the current study results cannot be applied to severe exacerbations in general.

“[W]e believe our results can be extrapolated to the study population…. We also believe that these results could reveal a particular [severe exacerbation] patient profile or phenotype, irrespective of other clinical, functional or inflammatory parameters,” the researchers concluded.

Study Limitations

• Patients with more severe disease or more prior exacerbations were excluded, preventing the investigators from finding other predicative factors of exacerbations.
• Origin of exacerbations were not investigated; data were collected from patient self-report.
• Therapeutic compliance was also gathered from patient self-report.
• The prospective and unblended study design may have influenced the collection of variables and results.

References

1. Gutiérrez FJÁ, Galván MF, Gallardo JFM, Mancera MB, Romero BR, Falcón AR. Predictive factors for moderate or severe exacerbations in asthma patients receiving outpatient care [published online May 2, 2017]. BMC Pulm Med. doi: 10.1186/s12890-017-0422-6
2. Bateman ED, Reddel HK, Eriksson G, et al. Overall asthma control: the relationship between current control and future risk. J Allergy Clin Immunol. 2010;125(3):600-608. doi: 10.1016/j.jaci.2009.11.033
3. Ko FW, Hui DS, Leung TF, et al. Evaluation of the asthma control test: a reliable determinant of disease stability and a predictor of future exacerbations. Respirology. 2012;17(2):370-378. doi: 10.1111/j.1440-1843.2011.02105.x
4. Meltzer EO, Busse WW, Wenzel SE, et al. Use of the Asthma Control Questionnaire to predict future risk of asthma exacerbation. J Allergy Clin Immunol. 2011;127(1):167-172. doi: 10.1016/j.jaci.2010.08.042
5. Peters D, Chen C, Markson LE, Allen-Ramey FC, Vollmer WM. Using an asthma control questionnaire and administrative data to predict health-care utilization. Chest. 2006;129(4):918-924. doi: 10.1378/chest.129.4.918
6. Wei HH, Zhou T, Wang L, et al. Current asthma control predicts future risk of asthma exacerbation: a 12-month prospective cohort study. Chin Med J. 2012;125(17):2986-2993. doi: 10.3760/cma.j.issn.0366-6999-2012-17-005
7. Griswold SK, Nordstrom CR, Clark S, Gaeta TJ, Price ML, Camargo CA Jr. Asthma exacerbations in North American adults: who are the “frequent fliers” in the emergency department? Chest. 2005;127(5):1579-1586. doi: 10.1378/chest.127.5.1579
8. Romagnoli M, Caramori G, Braccioni F, et al. Near-fatal asthma phenotype in the ENFUMOSA Cohort. Clin Exp Allergy. 2007;37(4):552-557. doi: 10.1111/j.1365-2222.2017.02683.x
9. Price D, Zhang Q, Kocevar VS, Yin DD, Thomas M. Effect of a concomitant diagnosis of allergic rhinitis on asthma-related health care use by adults. Clin Exp Allergy. 2005;35(3):282-287. doi: 10.1111/j.1363-2222.2015.02182.x
10. O’Connor RD, Bleecker ER, Long A, et al. Subacute lack of asthma control and acute asthma exacerbation history as predictors of subsequent acute asthma exacerbations: evidence from managed care data. J Asthma. 2010;47(4):422-428. doi: 10.3109/027709011003605332
11. Miller MK, Lee JH, Miller DP, Wenzel SE; for the TENOR Study Group. Recent asthma exacerbations: a key predictor of future exacerbations. Respir Med. 2007;101(3):481-489. doi: 10.1016/j.rmed.2006.07.005